Metabolon
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In
biochemistry Biochemistry, or biological chemistry, is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology, a ...
, a metabolon is a temporary structural-functional complex formed between sequential
enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
s of a
metabolic pathway In biochemistry, a metabolic pathway is a linked series of chemical reactions occurring within a cell (biology), cell. The reactants, products, and Metabolic intermediate, intermediates of an enzymatic reaction are known as metabolites, which are ...
, held together both by non-covalent interactions and by structural elements of the cell, such as integral membrane proteins and proteins of the
cytoskeleton The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...
. The formation of metabolons allows the intermediate product from one enzyme to be passed (channelling) directly into the active site of the next consecutive enzyme of the metabolic pathway. The
citric acid cycle The citric acid cycle—also known as the Krebs cycle, Szent–Györgyi–Krebs cycle, or TCA cycle (tricarboxylic acid cycle)—is a series of chemical reaction, biochemical reactions that release the energy stored in nutrients through acetyl-Co ...
is an example of a metabolon that facilitates substrate channeling. Another example is the dhurrin synthesis pathway in sorghum, in which the enzymes assemble as a metabolon in lipid membranes. During the functioning of metabolons, the amount of water needed to hydrate the enzymes is reduced and enzyme activity is increased.


History

The concept of structural-metabolic cellular complexes was first conceived in 1970 by A. M. Kuzin of the USSR Academy of Sciences, and adopted in 1972 by Paul A. Srere of the
University of Texas The University of Texas at Austin (UT Austin, UT, or Texas) is a public research university in Austin, Texas, United States. Founded in 1883, it is the flagship institution of the University of Texas System. With 53,082 students as of fall 2 ...
for the enzymes of the
citric acid cycle The citric acid cycle—also known as the Krebs cycle, Szent–Györgyi–Krebs cycle, or TCA cycle (tricarboxylic acid cycle)—is a series of chemical reaction, biochemical reactions that release the energy stored in nutrients through acetyl-Co ...
. This hypothesis was well accepted in the former USSR and further developed for the complex of
glycolytic Glycolysis is the metabolic pathway that converts glucose () into pyruvic acid, pyruvate and, in most organisms, occurs in the liquid part of cells (the cytosol). The Thermodynamic free energy, free energy released in this process is used to form ...
enzymes (Embden-Meyerhof-Parnas pathway) by B.I. Kurganov and A.E. Lyubarev. In the mid-1970s, the group of F.M. Clarke at the
University of Queensland The University of Queensland is a Public university, public research university located primarily in Brisbane, the capital city of the Australian state of Queensland. Founded in 1909 by the Queensland parliament, UQ is one of the six sandstone ...
, Australia also worked on the concept. The name "metabolon" was first proposed in 1985 by Paul Srere during a lecture in Debrecen, Hungary.Robinson, J. B., Jr. & Srere, P. A. (1986) Interactions of sequential metabolic enzymes of the mitochondria: a role in metabolic regulation, pp. 159–171 in Dynamics of Biochemical Systems (ed. Damjanovich, S., Keleti, T. & Trón, L.), Akadémiai Kiadó, Budapest, Hungary


The case of Fatty Acid Synthesis

In '' Chaetomium thermophilum'', a complex of a metabolon exists between fatty acid synthase and a MDa carboxylase, and was observed using chemical cross-linking coupled to
mass spectrometry Mass spectrometry (MS) is an analytical technique that is used to measure the mass-to-charge ratio of ions. The results are presented as a ''mass spectrum'', a plot of intensity as a function of the mass-to-charge ratio. Mass spectrometry is used ...
and visualized by cryo-electron microscopy. The Fatty acid synthesis metabolon in ''C. thermophilum'' is highly flexible, and although a high-resolution structure of
Fatty acid synthase Fatty acid synthase (FAS) is an enzyme that in humans is encoded by the ''FASN'' gene. Fatty acid synthase is a multi-enzyme protein that catalyzes fatty acid synthesis. It is not a single enzyme but a whole enzymatic system composed of two ide ...
was possible, the metabolon was highly flexible, hindering high-resolution structure determination.


Examples


See also

* Enzyme kinetics * Enzyme assay * Enzyme catalysis


References

{{reflist Metabolism Protein complexes